Induction of microglial and astrocytic response in the adult rat lumbar spinal cord following middle cerebral artery occlusion.

The response of microglia and astrocytes, as detected immunohistochemically by the monoclonal antibody OX-42 and anti-glial fibrillary acidic protein (GFAP) respectively, was studied in the rat lumbar spinal cord following focal cerebral ischaemia produced by permanent occlusion of the middle cerebral artery (MCA) above the rhinal fissure. At 1 and 2 days after right-sided MCA occlusion, OX-42 immunoreactivity of microglia in both the contralateral dorsal and ventral horns of the lumbar spinal cord was moderately increased compared with cells of the ipsilateral side. The microglial reaction was progressive, with some cells transformed into amoeboid form considered to be macrophages at day 3. By 5 days, many of the reactive microglia, notably in the ventral horn, appeared to encircle the soma of motoneurons. At 7 days, the microglial reaction had subsided while astrocytes in the same area were hypertrophied to replace the perineuronal microglia. The microglial response in both the cerebral cortex and lumbar spinal cord was effectively reduced by the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Present results suggest that following MCA occlusion, the vigorous response of microglia, and subsequently astrocytes, in the spinal cord in extra-focal areas far removed from the primary site of ischaemia may be mediated by glutamate released from the ischaemic corticospinal neurons through NMDA receptors on the postsynaptic spinal cord neurons.